The use and manufacture of oral enteric dosage forms are known in the art. Such dosage forms have been explained and reviewed in reference works, e.g., in Remington's Pharmaceutical Sciences, 18th edition, Mack Publishing Co., Easton, Pa. (1990). Enteric dosage forms are desirable, either to protect the content of the dosage form from the gastric conditions or to protect the gastric tissue from an irritant material contained in the enteric dosage form. The protection of gastric and esophageal tissues using enteric dosage forms is very important for the sustained use of non-steroidal anti-inflammatory drugs in conditions such as chronic pain, osteoarthritis, and rheumatoid arthritis.
A further use for enteric dosages is for the prevention of a lasting, unacceptable mouth odor resulting from ingestion of substances like garlic or fish oil. Furthermore, in some cases all-natural fish oil capsules containing omega-3 fatty acids are desirable to consumers.
Enteric dosage forms are also used to provide slow, controlled, or delayed release of a substance.
To fulfill the compendium definition requirement for enteric or gastro-resistant preparations, these preparations have to pass specific compendia tests. The enteric or gastro-resistant property is obtained only if the enteric dosage form does not dissolve or disintegrate in gastric acidity for a specified amount of time (usually two hours in 0.1 N hydrochloric acid, pH ca. 1.2 at 37° C.). Further, the enteric dosage forms must release their contents in simulated intestinal environments (e.g., in buffers of pH values at about 6.8) within certain time periods. Detailed evaluation techniques are described in national and international pharmacopoeia.
The majority, if not all, of the enteric dosage forms currently in use are produced by a film-coating process, where a thin film layer of acid-insoluble (enteric) polymer is accumulated on the surface of a pre-manufactured dosage form. Dosage forms coated in this manner have been mainly tablets and, to a lesser extent, hard or soft capsules. The enteric coating method involves spraying of an aqueous or organic solution or a suspension of enteric polymers onto tumbling or moving tablets or capsules, accompanied by drying using hot air.
Enteric dosage forms made by coating suffer from various process-related problems and defects that affect their performance or appearance. For example, “orange peel” surface formation, also known as surface roughness, mottling, or lack of surface homogeneity may result. In addition, coat integrity failure may occur, such as in cases of cracking or flaking of the coating. All coatings present inherent problems, including possible uneven distribution of the coating ingredients, which can easily happen under the multivariate coating process. These failures of enteric coatings reduce the effectiveness of said coating in preventing painful and often harmful gastric and esophageal disturbances.
The foregoing problems of enteric coatings are shared by all enteric dosage forms such as tablets and capsules. However, the problems faced during coating of capsules are even more critical, due to the delicate and heat sensitive nature of the soft elastic capsule shell. Both hard and soft capsules can easily undergo agglomeration and distortion due to the heat-sensitive shell composition. Moreover, the smoothness and elasticity of the capsule surface make it difficult to form an intact adhering enteric coat without careful sub-coating steps to improve the surface for coating. A further disadvantage of enteric coating for soft capsules is the loss of the normally shiny and clear appearance of capsule gelatin shells. The elegant, clear gelatin shell has been a significant reason for soft capsule popularity and acceptance. In addition to the undesirable surface texture modifications usually caused by coating, most accepted aqueous enteric polymer preparations result in opaque capsules.
Medical professionals are increasingly recognizing the positive cardiovascular health benefits of fish oil based products. The principle oral dosage of fish oil is through soft gelatin capsules. However, a major limitation for consumers and patient compliance for the continued taking of these fish oil products is the presence of disruptive and unpleasant fishy odors associated with these traditional soft gelatin fish oil capsules. In particular, taking fish oil can result in negative side effects, including but not limited to, gastric disturbances such as fishy eructation (belching, e.g., “fishy burps”), gastrointestinal discomfort, bloating, nausea, diarrhea, unpleasant fishy odor, or unpleasant fishy aftertaste.
To minimize these negative side effects, consumers often will freeze their fish oil capsules before ingestion, which is thought to potentially prevent break down of the capsule in the esophagus and stomach. Several commercial products offer enterically coated fish oil soft gelatin capsules to help circumvent capsule break down in the stomach. Other products include flavors or odor masking agents such as citrus or vanilla. However, these agents do not solve the negative side effects. In addition, there are significant problems associated with traditional enteric coated capsules.
In addition, consumers have expressed a desire for nutraceuticals or dietary supplements made of all-natural ingredients. Thus, compositions promoting “All-Natural Ingredients” are appealing to nutrition-conscious consumers compared to products containing artificial ingredients.
Accordingly, it is desirable to develop an oral delivery system that provides enteric properties and that utilize all-natural ingredients, especially for use with fish oil or non-steroidal anti-inflammatory drugs.
Therefore, the enteric oral soft capsules described herein, have robust acid-resistant capsule shells, and are not enterically coated. Moreover, the soft capsules described herein, are easy to ingest.